Studies are planned on the formation, metabolism and disposition of heme, hemoproteins and bile pigments in health and various forms of jaundice. The sites, mechanisms and rates of the conversion of heme to bilirubin will be identified and characterized, and the metabolic control of this process will be investigated. The role of heme in the regulation of its own biosynthesis will be elucidated, particularly in relation to drug metabolism and porphyrin formation in the liver. The chemical mechanism involved in the photodecomposition of bilirubin will be investigated and an attempt will be made to identify the decay products and to test their toxicity in cell culture and intact organisms. This information will be essential to decide whether phototherapy of newborn infants with hyperbilirubinemia is a safe procedure. In patients with Gilbert's syndrome, the rate of bilirubin formation will be studied in the fed and fasted state to determine the cause of the hyperbilirubinemia. Similar studies will be carried out in normal individuals before and after treatment with drugs that induced drug-metabolizing heme enzymes in the liver.